The invention relates to a method for producing 5-nitro-2-furfuryl acetate from furfuryl acetate and a mixture of strong nitric acid and acetic anhydride. The 5-nitro-2-furfuryl acetate produced by the method according to the invention can as such be used as a biologically active agent against, for example, molds, fungi or bacteria, or as an intermediate in the production of such agents.
The manufacture of 5-nitro-2-furfuryl acetate by nitrating either furfuryl acetate or furfuryl alcohol is previously known [H. Gilman, C. F. Wright, J. Amer. Chem. Soc. 53 (1931), pp. 1923-4]. A mixture of acetic anhydride and fuming nitric acid is used as the nitrating agent. The intermediate formed in the reaction is decomposed by means of pyridine. The use of furfuryl alcohol instead of furfuryl acetate would seem advantageous since one unnecessary production stage, i.e., the esterification of furfuryl alcohol, would be thereby eliminated. However, the method cannot be used on a large scale since 5-nitro-2-furfuryl nitrate, which is an unstable compound, is produced as a by-product. It may explode when it is, for example, hydrolyzed. The formation of this nitrate is mentioned even in the above article. The nitration of furan derivates by H. Gilman's method has been found inconvenient and even dangerous owing to the use of fuming nitric acid. Thus, a general method has later been introduced for the nitration of furan and its derivates (U.S. Pat. No. 2,490,006). It is noted therein that acetic anhydride must be present in a quantity of at least 4 mole, preferably 7.6 mole, and approx. 70-percent nitric acid in a quantity of 1-4 mole, preferably somewhat over 1 mole, per one mole furan derivate. According to the example, the nitration can be performed at 25.degree.-50.degree. C., preferably 40.degree..+-.3.degree. C. The decomposition of the intermediate can be performed by adding some base and by heating the mixture, the pH of which is 1.79-4.66, preferably 3.7, at 25.degree.-60.degree. C., preferably 55.degree. C., after the addition, until the conversion is complete. The main object is to protect the manufacture of 5-nitro-2-furfural diacetate used as a pharmaceutical raw material, in which case the substance to be nitrated is furfural or its diacetate. For this reason the conditions described in the patent do not correspond, in terms of economy and production techniques, to the optimal ones for nitrating furfuryl acetate. It should also be noted that the yield percentages cited in the patent do not give a correct picture since in several cases they represent only crude yields.
The nitration of furan derivates has also been treated in scientific literature. Thus, H. Saikachi et al. [J. Pharm. Soc. Japan 73 (1953), pp. 1132-6] in their investigations of the nitration of furfuryl acetate obtained a yield of 46% without a catalyst and in the best case 78% when using orthophosphoric acid as a catalyst. It should be noted that the melting point of the final product was only 38.degree.-44.degree. C., which corresponds to a concentration of approx. 90%, and thus it can be estimated that the best yield was approx. 70%. It should also be noted that nitric acid with a concentration of over 70% (d= 1.44 g/ml) and a reaction temperature of -25.degree. C. were used for the nitration. T. Sasaki [Bull. Inst. Chem. Research, Kyoto Univ. 33 (1955), pp. 39-48] obtained 60% as his best yield in nitrating furfuryl acetate, when using a reaction temperature of -25.degree. C. and sulfuric acid as the catalyst. The said methods are not economical owing to the low reaction temperature. It should be noted that the use of nitric acid with a concentration of over 70% necessitates the said low reaction temperature, and the reactions cannot be performed safely at normal temperatures, e.g., 0.degree.-20.degree. C.
P. Krkoska et al. [Chem. Listy 62 (1968), pp. 182-196] have presented a consistent study on the nitration of furan derivates. According to their study, the nitration of, for example, furfuryl acetate, occurs as follows: ##STR1##
According to the above factors, the yield is substantially dependent on the furan derivate in question. Thus, it can be said that in the nitration of furfural or its diacetate the yields are qualitatively better than in the nitration of furfuryl acetate.
Nevertheless, the reactions are not this simple. On the one hand it is not known what the nitrating agent actually is and it has been claimed that the catalyzing effect of acids is based on the formation of protonized acetyl nitrate [F. G. Bordwell, E. W. Garbisch Jr., J. Amer. Chem. Soc. 82 (1960), pp. 3588-3598]. On the other hand, it is noted in the article by the Czechoslovakians that it has been possible to isolate 3 different intermediates in nitrating furfural.
In our studies we observed deviating from previous practice that furfuryl acetate can be nitrated economically and with a good yield without catalysts; the use of catalysts also increases the waste water load (e.g., phosphoric acid) and complicates the control of the process by promoting oxidation reactions. By the method developed by us, yields of over 75% can be obtained, calculated as pure product.